Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain. METHODS: A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis. RESULTS: Nine studies (n = 863) were included (five randomized controlled trials [RCTs], two open-label non-comparative studies and two comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of three RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% confidence interval [CI]: -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI: -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain. CONCLUSIONS: While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine's role, if any, in pain medicine.

Efficacy and Safety of Magnesium for the Management of Chronic Pain in Adults: A Systematic Review.

Chronic pain is a highly prevalent and complex health problem that is associated with a heavy symptom burden, substantial economic and social impact, and also, very few highly effective treatments. This review examines evidence for the efficacy and safety of magnesium in chronic pain. The previously published protocol for this review was registered in International Prospective Register of Systematic Reviews (PROSPERO), MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched until September 2018. We included randomized controlled trials (RCTs) comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain measures. A total of 9 RCTs containing 418 participants were included. Three studies examined neuropathic pain (62 participants), 3 examined migraines (190 participants), 2 examined complex regional pain syndrome (86 participants), and 1 examined low back pain with a neuropathic component (80 participants). Heterogeneity of included studies precluded any meta-analyses. No judgment could be made about safety because adverse events were inconsistently reported in the included studies. Evidence of analgesic efficacy from included studies was equivocal. However, reported efficacy signals in some of the included trials provide a rationale for more definitive studies. Future, larger-sized trials with good assay sensitivity and better safety assessment and reporting, as well as careful attention to formulations with optimal bioavailability, will serve to better define the role of magnesium in the management of chronic pain.

Parkinson's pain is more aching and interfering with social life in Caucasians compared to Indians.

Objectives: Although there have been numerous studies conducted to better understand Parkinson's disease (PD), the epidemiology of its debilitating non-motor symptoms across different ethnicities remains understudied. Herein we explore the relationship between depression, anxiety and pain in PD patients of Caucasian or Indian ethnicity (PD Caucasians and PD Indians). Patients and Methods: All patients and healthy age and gender matched controls were assessed via semi-structured interviews for anxiety, pain and depression using structured questionnaires. Results: PD Indians did not differ from PD Caucasians on anxiety or depression. However, PD Caucasians were more likely to report aching pain by 80 times and dull pain by 108 times compared to PD Indians. PD Indians were 82% less likely to have pain interfering with social activities, and 90% less likely to have pain interfering with relations with others compared to PD Caucasians. Conclusion: Although an Indo-Caucasian difference may not be detected from mood dysfunction, important differences may exist from the influence of pain interfering with several dimensions of life.

Optimizing GRID and Lattice Spatially Fractionated Radiation Therapy: Innovative Strategies for Radioresistant and Bulky Tumor Management.

Treating radioresistant and bulky tumors is challenging due to their inherent resistance to standard therapies and their large size. GRID and lattice spatially fractionated radiation therapy (simply referred to GRID RT and LRT) offer promising techniques to tackle these issues. Both approaches deliver radiation in a grid-like or lattice pattern, creating high-dose peaks surrounded by low-dose valleys. This pattern enables the destruction of significant portions of the tumor while sparing healthy tissue. GRID RT uses a 2-dimensional pattern of high-dose peaks (15-20 Gy), while LRT delivers a three-dimensional array of high-dose vertices (10-20 Gy) spaced 2-5 cm apart. These techniques are beneficial for treating a variety of cancers, including soft tissue sarcomas, osteosarcomas, renal cell carcinoma, melanoma, gastrointestinal stromal tumors (GISTs), pancreatic cancer, glioblastoma, and hepatocellular carcinoma. The specific grid and lattice patterns must be carefully tailored for each cancer type to maximize the peak-to-valley dose ratio while protecting critical organs and minimizing collateral damage. For gynecologic cancers, the treatment plan should align with the international consensus guidelines, incorporating concurrent chemotherapy for optimal outcomes. Despite the challenges of precise dosimetry and patient selection, GRID RT and LRT can be cost-effective using existing radiation equipment, including particle therapy systems, to deliver targeted high-dose radiation peaks. This phased approach of partial high-dose induction radiation therapy with standard fractionated radiation therapy maximizes immune modulation and tumor control while reducing toxicity. Comprehensive treatment plans using these advanced techniques offer a valuable framework for radiation oncologists, ensuring safe and effective delivery of therapy for radioresistant and bulky tumors. Further clinical trials data and standardized guidelines will refine these strategies, helping expand access to innovative cancer treatments.

Sphincter-sparing surgery for adenocarcinoma of the distal 3 cm of the true rectum: results after neoadjuvant therapy and minimally invasive radical surgery or local excision.

BACKGROUND: Ideal treatment of rectal cancer includes controlling the cancer; minimizing trauma, morbidity, and mortality; and avoiding a colostomy with preservation of adequate function. These goals become more challenging the further distal in the rectum the cancer is located. We sought to determine whether minimally invasive sphincter-preservation surgery (SPS) can accomplish good cancer control, maintaining sphincter function with minimal morbidity and mortality in rectal cancers of the distal 3 cm after receiving neoadjuvant chemoradiotherapy. METHODS: We retrospectively reviewed a prospectively maintained rectal cancer database of a single colorectal surgeon to identify all patients with cancers of the distal 3 cm undergoing SPS via a laparoscopic total mesorectal excision or transanal endoscopic microsurgery (TEM). All patients received neoadjuvant chemoradiotherapy. Patient data, including demographics, initial tumor characteristics, staging, radiation dose, perioperative morbidity and mortality, and local recurrence (LR) and survival, were analyzed. RESULTS: A total of 161 patients (108 men) underwent SPS via 3 techniques: transanal abdominal transanal proctosigmoidectomy (TATA, n = 106), TEM (n = 49), or ultralow anterior resection (LAR, n = 6). Average age was 62 years (range 22-90 years). The mean levels in rectum from the anorectal ring were as follows: TATA, 1.3 cm (range -1.0 to 3.0 cm), TEM, 1.5 cm (range -0.5 to -3.0 cm), and LAR, 2.9 cm (range 2.5-3.0 cm) (p > 0.05). Preoperative T stage was as follows: T3, n = 108 (TATA 83, TEM 20, LAR 5), T2, n = 48 (TATA 22, TEM 25, LAR 1), T1, n = 3 (TATA 1, TEM 2), and T4, n = 2 (both TEM). All patients received concomitant 5-fluorouracil-based chemotherapy and radiotherapy (mean, 5300 cGy; range 3,000-7,295 cGy). The mean estimated blood loss was 376 ml (range 10-3,600 ml). There were no mortalities. Morbidity rates were as follows: LAR, 0; TATA, 13.2%; and TEM, 32 % (wound disruption: major, 10%; minor, 16%). Pathologic staging was as follows: ypCR: uT2, 34%, and uT3, 19%. Overall LR was 3.7%. By procedure, the follow-up, LR, and KM5YAS, respectively, were: TATA, 37.9 months, 3 and 95%; TEM, 36.3 months, 6 and 88%; and LAR, 63.1 months, 0 and 75% (p > 0.05). CONCLUSIONS: This study demonstrates positive oncologic outcomes, low LR rates, and high KM5YS after minimally invasive SPS. A colostomy-free lifestyle and cancer control make the minimally invasive surgical approach an excellent treatment option for complex distal rectal cancers.

Prevalence of postoperative pain after hospital discharge: systematic review and meta-analysis.

Assessment and management of postoperative pain after hospital discharge is very challenging. We conducted a systematic review to synthesize available evidence on the prevalence of moderate-to-severe postoperative pain within the first 1 to 14 days after hospital discharge. The previously published protocol for this review was registered in PROSPERO. MEDLINE and EMBASE databases were searched until November 2020. We included observational postsurgical pain studies in the posthospital discharge setting. The primary outcome for the review was the proportion of study participants with moderate-to-severe postoperative pain (eg, pain score of 4 or more on a 10-point Numerical Rating Scale) within the first 1 to 14 days after hospital discharge. This review included 27 eligible studies involving a total of 22,108 participants having undergone a wide variety of surgical procedures. The 27 studies included ambulatory surgeries (n = 19), inpatient surgeries (n = 1), both ambulatory and inpatient surgeries (n = 4), or was not specified (n = 3). Meta-analyses of combinable studies provided estimates of pooled prevalence rates of moderate-to-severe postoperative pain ranging from 31% 1 day after discharge to 58% 1 to 2 weeks after discharge. These findings suggest that moderate-to-severe postoperative pain is a common occurrence after hospital discharge and highlight the importance of future efforts to more effectively evaluate, prevent, and treat postsurgical pain in patients discharged from the hospital.

Genetic Analysis of the Single-Nucleotide Polymorphisms rs880810, rs545793, rs80094639, and rs13251901 in Nonsyndromic Oral Clefts: A Case-Parent Trio Study.

Oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are the most common types of congenital anomalies of the human face. Various genetic and environmental factors play a role in developing oral clefts. Several studies have shown the association of the PAX7 gene and the 8q24 region with these oral clefts in different populations worldwide. However, there are no reported studies on the possible connection between the PAX7 gene and the 8q24 region nucleotide variants and the risk of developing nonsyndromic oral clefts (NSOC) in the Indian population. Hence, this study aimed to test the possible association between PAX7 gene single-nucleotide polymorphisms (SNPs) rs880810, rs545793,rs80094639, and rs13251901 of the 8q24 region using a case-parent trio design. Forty case-parent trios were selected from the CLP center. Genomic DNA was isolated from the cases and their parents. The rs880810, rs545793, rs80094639, and rs13251901 were genotyped by the MassARRAY technique. PLINK software was used for statistical analysis. All the SNPs were tested for Hardy-Weinberg equilibrium. No statistical significance was found with any SNPs, as none of the genotyped SNPs showed a p -value of less than 0.05. Hence, the rs880810, rs545793, and rs80094639 of the PAX7 gene, and rs13251901 of the 8q24 region are not associated with NSOC in the Indian population.

Streeter's Syndrome of Lower Limb Associated with CTEV.

Introduction: The term Streeter's syndrome is a term used to describe rare congenital malformations that includes a variety of clinical presentations usually consisting of a constriction band around a part of the body which can be as superficial as involving just the skin which can be only cosmetic and asymptomatic or can be as deep as causing restricted circulation distally which may be in incompatible with life. Such conditions are remarkably rare accounting for an incidence range from 1:1.2 k to 1: 15 k live births and 178:10 k spontaneous abortions [1]. Males and females are uniformly affected. Almost all cases are sporadic; extremely rare evidence of familial transmission. The entity has been described in the literature in 34 different terms, (such as amniotic rupture sequence, ADAM complex, constriction band syndrome, Streeter's dysplasia, etc.) due to its extremely variable clinical features and lack of understanding of the etiology. This results in a lack of understanding and creates unnecessary stress for the surgeon/physician as well as the parents. Case Report: We discuss case reports of two such cases with their simple nature of treatment with their outcomes. Conclusion: There is a significant deficit in the education of cases with low incidence, such is the case with pediatric patients presenting with amniotic bands, which usually present and are associated with Congenital Talipes Equino Varus deformity. In such cases, improper or incorrect treatment and/or neglect of the constriction may lead to the vascular deficit and eventually auto-amputation of the segment distal to the amniotic band.

Neoadjuvant concurrent chemoradiotherapy using infusional gemcitabine in locally advanced rectal cancer: A phase II trial.

INTRODUCTION: Gemcitabine is a well-known radiosensitizer. Herein, we tested the efficacy and toxicity of preoperative concurrent infusional gemcitabine and radiotherapy in locally advanced rectal cancer. PATIENTS AND METHODS: This was a phase II, single-arm trial. Eligible patients had a diagnosis of rectal adenocarcinoma with clinical stage T3-T4 and/or nodal involvement, age ≥18 years, and no prior chemotherapy or radiotherapy. Patients received preoperative radiation at a dose of 50.4-54 Gy over 28 days with concurrent infusional gemcitabine administered at a dose of 100 mg/m2 over the course of 24 h weekly for 6 weeks. The primary endpoint was pathological complete response (pCR). RESULTS: Forty patients were recruited. Only one patient did not complete therapy due to death. Eight patients did not undergo surgery, one died, two progressed to nonresectable disease, and five withdrew consent. Five patients progressed prior to surgery, with two having unresectable metastases and three having resectable liver metastases. One was found to have peritoneal metastasis during surgery. Out of the 32 patients who underwent surgery, seven achieved pCR at a rate of 20%. With a median follow-up of 30 months, four additional patients had a distant relapse (one had a subsequent local relapse). The 3-year event-free and overall survival rates were 70% and 85%, respectively. The commonest preoperative grade 3-4 toxicity included lymphopenia (50%), neutropenia (41%), anemia (15%), diarrhea (12%), abdominal pain (12%), and proctitis (8%). CONCLUSION: Concurrent preoperative chemoradiotherapy using infusional gemcitabine for locally advanced rectal cancer achieved an encouraging degree of local control with manageable toxicity.

An International Consensus on the Design of Prospective Clinical-Translational Trials in Spatially Fractionated Radiation Therapy.

PURPOSE: Spatially fractionated radiation therapy (SFRT), which delivers highly nonuniform dose distributions instead of conventionally practiced homogeneous tumor dose, has shown high rates of clinical response with minimal toxicities in large-volume primary or metastatic malignancies. However, prospective multi-institutional clinical trials in SFRT are lacking, and SFRT techniques and dose parameters remain variable. Agreement on dose prescription, technical administration, and clinical and translational design parameters for SFRT trials is essential to enable broad participation and successful accrual to rigorously test the SFRT approach. We aimed to develop a consensus for the design of multi-institutional clinical trials in SFRT, tailored to specific primary tumor sites, to help facilitate development and enhance the feasibility of such trials. METHODS AND MATERIALS: Primary tumor sites with sufficient pilot experience in SFRT were identified, and fundamental trial design questions were determined. For each tumor site, a comprehensive consensus effort was established through disease-specific expert panels. Clinical trial design criteria included eligibility, SFRT technology and technique, dose and fractionation, target- and normal-tissue dose parameters, systemic therapies, clinical trial endpoints, and translational science considerations. Iterative appropriateness rank voting, expert panel consensus reviews and discussions, and public comment posting were used for consensus development. RESULTS: Clinical trial criteria were developed for head and neck cancer and soft-tissue sarcoma. Final consensus among the 22 trial design categories each (a total of 163 criteria) was high to moderate overall. Uniform patient cohorts of advanced bulky disease, standardization of SFRT technologies and dosimetry and physics parameters, and collection of translational correlates were considered essential to trial design. Final guideline recommendations and the degree of agreement are presented and discussed. CONCLUSIONS: This consensus provides design guidelines for the development of prospective multi-institutional clinical trials testing SFRT in advanced head and neck cancer and soft-tissue sarcoma through in-advance harmonization of the fundamental clinical trial design among SFRT experts, potential investigators, and the SFRT community.

The association of age with acute toxicities in NRG oncology combined modality lower GI cancer trials.

PURPOSE: Expected toxicity from chemoradiation (CRT) is an important factor in treatment decisions but is poorly understood in older adults with lower gastrointestinal (GI) malignancies. Our objective was to compare acute adverse events (AAEs) of older and younger adults with lower GI malignancies treated on NRG studies. METHODS: Data from 6 NRG trials, testing combined modality therapy in patients with anal or rectal cancer, were used to test the hypothesis that older age was associated with increased AAEs. AAEs and compliance with protocol-directed therapy were compared between patients aged ≥70 and < 70. Categorical variables were compared across age groups using the chi-square test. The association of age on AAEs was evaluated using a covariate-adjusted logistic regression model, with odds ratio (OR) reported. To adjust for multiple comparisons, a p-value <0.01 was considered statistically significant. RESULTS: There were 2525 patients, including 380 patients ≥70 years old (15%) evaluable. Older patients were more likely to have worse baseline performance status (PS 1 or 2) (23% vs. 16%, p = 0.001), but otherwise baseline characteristics were similar. Older patients were less likely to complete their chemotherapy (78% vs. 87%, p < 0.001), but had similar RT duration. On univariate analysis, older patients were more likely to experience grade ≥ 3 GI AAEs (36% vs. 23%, p < 0.001), and less likely to experience grade ≥ 3 skin AAEs (8% vs. 14%, p = 0.002). On multivariable analysis, older age was associated with grade ≥ 3 GI AAE (OR 1.93, 95% CI: 1.52, 2.47, p < 0.001) after adjusting for sex, race, PS, and disease site. CONCLUSIONS: Older patients with lower GI cancers who underwent CRT were less likely to complete chemotherapy and had higher rates of grade 3+ GI AAEs. These results can be used to counsel older adults prior to treatment and manage expected toxicities throughout pelvic CRT.

An International Consensus on the Design of Prospective Clinical-Translational Trials in Spatially Fractionated Radiation Therapy for Advanced Gynecologic Cancer.

Despite the unexpectedly high tumor responses and limited treatment-related toxicities observed with SFRT, prospective multi-institutional clinical trials of SFRT are still lacking. High variability of SFRT technologies and methods, unfamiliar complex dose and prescription concepts for heterogeneous dose and uncertainty regarding systemic therapies present major obstacles towards clinical trial development. To address these challenges, the consensus guideline reported here aimed at facilitating trial development and feasibility through a priori harmonization of treatment approach and the full range of clinical trial design parameters for SFRT trials in gynecologic cancer. Gynecologic cancers were evaluated for the status of SFRT pilot experience. A multi-disciplinary SFRT expert panel for gynecologic cancer was established to develop the consensus through formal panel review/discussions, appropriateness rank voting and public comment solicitation/review. The trial design parameters included eligibility/exclusions, endpoints, SFRT technology/technique, dose/dosimetric parameters, systemic therapies, patient evaluations, and embedded translational science. Cervical cancer was determined as the most suitable gynecologic tumor for an SFRT trial. Consensus emphasized standardization of SFRT dosimetry/physics parameters, biologic dose modeling, and specimen collection for translational/biological endpoints, which may be uniquely feasible in cervical cancer. Incorporation of brachytherapy into the SFRT regimen requires additional pre-trial pilot investigations. Specific consensus recommendations are presented and discussed.

Low-dose abdominal radiation as a docetaxel chemosensitizer for recurrent epithelial ovarian cancer: a phase I study of the Gynecologic Oncology Group.

OBJECTIVES: The aim of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of whole abdomen radiation as a chemosensitizer of weekly docetaxel for women with recurrent epithelial ovarian fallopian tube, or peritoneal cancers. PATIENTS AND METHODS: Women were enrolled on one of three dose levels of docetaxel (20, 25, or 30 mg/m(2)) administered weekly with concurrent low-dose whole abdominal radiation given as 60 cGy bid 2 days weekly for a total of 6 weeks. RESULTS: Thirteen women were enrolled and received 70 weekly treatments of docetaxel in combination with radiation therapy. At the first dose level, docetaxel 25mg/m(2), grade 3 fatigue and thrombocytopenia were observed. At the next dose level, docetaxel 30 mg/m(2), grade 3 febrile neutropenia, grade 4 thrombocytopenia with epistaxis, and grade 3 diarrhea were observed. Given these dose-limiting toxicities, a lower dose of docetaxel 20mg/m(2) was administered and found to be tolerable. No objective responses were observed among the 10 patients with measurable disease; however, the median progression-free survival (PFS) in all patients was 3.3 months, and 3 of the patients with measurable disease were free of tumor progression after 6 months (30%; 90% confidence interval 8.7-61%). CONCLUSIONS: Twice weekly low-dose whole abdomen radiation during weekly docetaxel 20 mg/m(2) was well-tolerated. Given the PFS demonstrated in these women with resistant ovarian cancer, further study of whole abdominal radiation and concurrent chemotherapy may be warranted.

Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data.

BACKGROUND: Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. METHODS: In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. FINDINGS: 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors. INTERPRETATION: Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. FUNDING: None.

Effects of tree species diversity and stand structure on carbon stocks of homestead forests in Maheshkhali Island, Southern Bangladesh.

BACKGROUND: The homestead forests of Bangladesh occupy 0.27 million hectares (10% of the total forested area) and have potential to store carbon (C) and conserve biodiversity. Small scale forestry practices, however, are lacking reliable estimation of C stocks and tree species diversity. This may hinder successful implementation of REDD + and similar mechanisms as they concentrate on large-scale forests. This study aimed to estimate the above- and below-ground carbon stocks in homestead forests of Maheshkhali Island in Bangladesh and how tree species diversity and stand structural variation affect these C stocks. We randomly surveyed a total of 239 homestead forests in the hillside, beachside, and inland in 2019. RESULTS: Tree biomass C stocks were 48-67% greater in the inland and hillside forests than in the beachside due to significantly greater stand density, basal area, tree diameter. In total we found 52 tree species, but most abundant species in the inland and hillside forests, Mangifera indica, Samanea saman, and Artocarpus heterophyllus stored the most C in tree biomass. Greater tree species richness and diversity index in the inland and hillside forests indicated greater above- and below-ground tree biomass C stocks. An increase in tree species richness and diversity index by one unit was found to increase the tree biomass C stock by 22 and 30 Mg C ha-1, respectively. The total soil C stock was also affected by tree species diversity, stand density, and their interaction with soil properties. Total soil C stocks were greatest (51 Mg ha-1) in the inland forests, having also the greatest stand density and tree species richness. C stock in soil surface was greatest in the hillside forests due to the greatest litterfall, but the average share of litterfall from the total biomass C was only 0.1%. CONCLUSIONS: Homestead forest ecosystems could store 96 Mg C ha-1 in total, which can contribute to climate change mitigation by generating C credits for small-scale homestead forests owners. Above- and below-ground tree biomass C stocks were found to correlate with tree species diversity, which may also contribute to biodiversity conservation in the REDD + in Bangladesh and countries alike.

Efficacy and Safety of Drug Combinations for Chronic Pelvic Pain: Protocol for a Systematic Review.

BACKGROUND: Chronic pelvic pain with various etiologies and mechanisms affects men and women and is a major challenge. Monotherapy is often unsuccessful for chronic pelvic pain, and combinations of different classes of medications are frequently prescribed, with the expectation of improved outcomes. Although a number of combination trials for chronic pelvic pain have been reported, we are not aware of any systematic reviews of the available evidence on combination drug therapy for chronic pelvic pain. OBJECTIVE: We have developed a protocol for a systematic review to evaluate available evidence of the efficacy and safety of drug combinations for chronic pelvic pain. METHODS: This systematic review will involve a detailed search of randomized controlled trials investigating drug combinations to treat chronic pelvic pain in adults. The databases searched will include the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from their inception until the date the searches are run to identify relevant studies. The primary outcome will be pain relief measured using validated scoring tools. Secondary outcomes, where reported, will include the following: adverse events, serious adverse events, sexual function, quality of life, and depression and anxiety. Methodological quality of each included study will be assessed using the Cochrane Risk of Bias Tool. RESULTS: The systematic review defined by this protocol is expected to synthesize available good quality evidence on combination drug therapy in chronic pelvic pain, which may help guide future research and treatment choices for patients and their health care providers. CONCLUSIONS: This review will provide a clearer understanding of the efficacy and safety of combination pharmacological therapy for chronic pelvic pain. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020192231; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=192231. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/21909.

General risks of harm with cannabinoids, cannabis, and cannabis-based medicine possibly relevant to patients receiving these for pain management: an overview of systematic reviews.

ABSTRACT: The growing demand for improved pain treatments together with expanding legalization of, and access to, cannabinoids, cannabis, and cannabis-based medicines has intensified the focus on risk-benefit considerations in pain management. Given limited harms data from analgesic clinical trials, we conducted an overview of systematic reviews focused on all harms possibly relevant to patients receiving cannabinoids for pain management. This PROSPERO-registered, PRISMA-compliant systematic overview identified 79 reviews, encompassing over 2200 individual reports about psychiatric and psychosocial harms, cognitive/behavioral effects, motor vehicle accidents, cardiovascular, respiratory, cancer-related, maternal/fetal, and general harms. Reviews, and their included studies, were of variable quality. Available evidence suggests variable associations between cannabis exposure (ranging from monthly to daily use based largely on self-report) and psychosis, motor vehicle accidents, respiratory problems, and other harms. Most evidence comes from settings other than that of pain management (eg, nonmedicinal and experimental) but does signal a need for caution and more robust harms evaluation in future studies. Given partial overlap between patients receiving cannabinoids for pain management and individuals using cannabinoids for other reasons, lessons from the crisis of oversupply and overuse of opioids in some parts of the world emphasize the need to broadly consider harms evidence from real-world settings. The advancement of research on cannabinoid harms will serve to guide optimal approaches to the use of cannabinoids for pain management. In the meantime, this evidence should be carefully examined when making risk-benefit considerations about the use of cannabinoids, cannabis, and cannabis-based medicine for chronic pain.

International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management.

ABSTRACT: The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.

Prevalence of Postoperative Pain Following Hospital Discharge: Protocol for a Systematic Review.

BACKGROUND: Pain is one of the most common, feared, and unpleasant symptoms associated with surgery. However, there is a clear gap in patient care after surgical patients are discharged from hospital, resulting in poorly controlled postoperative pain. Inadequate pain management after discharge can have detrimental effects on quality of life and lead to the development of chronic postsurgical pain. The severity of postoperative pain before discharge is well described, but less emphasis has been placed on assessing pain at home after hospital discharge. OBJECTIVE: The objective of this review is to summarize the prevalence of moderate-to-severe postoperative pain within the first 1 to 14 days after hospital discharge. METHODS: A detailed search of epidemiological studies investigating postoperative pain will be conducted on MEDLINE and EMBASE from their inception until the date the searches are run. The primary outcome will be the proportion of patients reporting moderate-to-severe postoperative pain at rest and with movement within the first 1 to 14 days after hospital discharge. The secondary outcomes will include a comparison of postoperative pain after discharge between patients who underwent ambulatory and inpatient surgery, and adverse outcomes attributable to poor pain control after hospital discharge (eg, readmission to hospital, emergency room or other unplanned medical visits, or a decrease in quality of life). RESULTS: The protocol has been registered in PROSPERO (registration number CRD42020194346). The search strategies for MEDLINE and EMBASE have been completed. The final results are expected to be published in May 2021. CONCLUSIONS: This systematic review is expected to synthesize evidence describing the prevalence of postoperative pain after hospital discharge. Available epidemiological evidence may help inform the magnitude of the problem of postoperative pain at home after hospital discharge. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020194346; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=194346. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/22437.